Abstract
Ketopiperazine 2 was designed from a previously published analog. Compound 2 was shown to be a novel, potent inhibitor of renin that, when administered orally, lowered blood pressure in a hypertensive double transgenic (human renin and angiotensinogen) mouse model. Compound 2 was further optimized to sub-nanomolar potency by designing an analog that addressed the S3 sub-pocket of the renin enzyme (16).
MeSH terms
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Animals
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Blood Pressure / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Mice
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Mice, Transgenic
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Molecular Structure
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Piperazines / chemical synthesis
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Piperazines / chemistry
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Piperazines / pharmacology*
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Renin / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Piperazines
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Renin